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PERSPECTIVES ON CARE CLINICIANS CORNER

AT THE CLOSE OF LIFE

Spinal Cord Compression in Patients


With Advanced Metastatic Cancer
All I Care About Is Walking and Living My Life
Janet L. Abrahm, MD
As 1 of the 12 700 US cancer patients who, each year, de-
Michael B. Banffy, MD
velops metastatic spinal cord compression, Ms H wishes to
Mitchel B. Harris, MD walk and live her life. Sadly, this wish may be difficult to fulfill.
THE PATIENTS STORY Before diagnosis, 83% to 95% of patients experience back
Ms H is a 56-year-old interventional radiology technician liv- pain, which often is referred, obscuring the site(s) of the com-
ing alone in a 2-story house. In 1986, she developed breast can- pression(s). Prediction of ambulation depends on a patients
cer,initiallytreatedbyleftmastectomyfollowedbychemotherapy ambulatory status before therapy and time between devel-
and chest wall radiotherapy. In 1990, she developed bony me- oping motor defects and starting therapy. Ambulatory pa-
tastases. Bisphosphonates were initiated and a left rib resection tients with no visceral metastases and more than 15 days
done; after a salpingo-oophorectomy, she had regression of a between developing motor symptoms and receiving therapy
left hip metastasis. In 2000, a T7 vertebral metastasis was treated have the best rate of survival. To preserve ambulation and
with 44 Gy to the T6 to T8 vertebral area. In 2004, a recurrent
optimize survival, magnetic resonance imaging should be
lesion required T7 vertebral corpectomy with structural rib au-
tograft and a T4 to T10 instrumented fusion. Capecitabine was performed for cancer patients with new back pain despite
begun and continued through November 2006, when she de- normal neurological findings. At diagnosis, counseling, pain
veloped thoracic pain and progressive difficulty walking. The management, and corticosteroids are begun. Most patients
T7 vertebral tumor now involved the T6 to T7 ventral epidu- are offered radiation therapy. Surgery followed by radiation
ral space with significant cord impingement. The posterior spi- is considered for selected patients with a single high-grade
nal fixation had loosened, and she had progressive deformity epidural lesion caused by a radioresistant tumor who also
of her spine. Ms Hs original surgeon, Dr L, recommended sur-
have an estimated survival of more than 3 months. Team
gery by Dr O followed by stereotactic radiosurgery (1500 cen-
tigray in 5 fractions over 5 days) at a university hospital 400 discussions with the patient and support network help de-
miles from her home. Ms H agreed. termine therapy options and include patient goals; assess-
On admission, she had difficulty with her gait and with ment of risks, benefits, and burdens of each treatment; and
urinary retention and had episodes of overflow urinary in- discussion of the odds of preserving prognosis of ambula-
continence. Her midthoracic pain was incapacitating de- tion and of the effect of therapy on the patients overall prog-
spite a transdermal fentanyl patch and oral rescue opioids. nosis. Rehabilitation improves impaired function and its
She was largely confined to bed but ambulated to the bath- associated depression. Clinicians can help patients cope with
room holding onto walls and using a walker.
transitions in self-image, independence, family and com-
On physical examination, Ms H was distraught. She had
a left mastectomy scar and postradiation chest wall changes. munity roles, and living arrangements and can help patients
She walked with an ataxic gait and had increased tone in with limited prognoses identify their end-of-life goals and
the lower limbs bilaterally. Her motor examination was re- preferences about resusitation and entering hospice.
markable for 4 of 5 strength in the left extensor hallucis lon- JAMA. 2008;299(8):937-946 www.jama.com
gus, tibialis anterior, and bilaterally in her iliopsoas muscles.
Author Affiliations are listed at the end of this article.
Sensation was decreased in the left first toe web, and there Corresponding Author: Janet L. Abrahm, MD, Dana-Farber Cancer Institute, 44
Binney St SW, 420, Boston, MA 02115 (jabrahm@partners.org).
See also Patient Page. Perspectives on Care at the Close of Life is produced and edited at the University
of California, San Francisco, by Stephen J. McPhee, MD, Michael W. Rabow, MD,
CME available online at www.jamaarchivescme.com and Steven Z. Pantilat, MD; Amy J. Markowitz, JD, is managing editor.
and questions on p 967. Perspectives on Care at the Close of Life Section Editor: Margaret A. Winker, MD,
Deputy Editor.

2008 American Medical Association. All rights reserved. (Reprinted) JAMA, February 27, 2008Vol 299, No. 8 937

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MALIGNANT SPINAL CORD COMPRESSION

was loss of proprioception bilaterally. Knee and ankle jerks Back pain is the most common symptom of spinal cord
were hyperactive and symmetrical; there were 3 beats of clo- compression, noted by 83% to 95% of patients prior to its
nus bilaterally, with a positive Babinski sign on the left foot. diagnosis.3,4 Pain, which can be local, referred, radicular, or
Following administration of preoperative medications, in- all 3 is caused by the expanding tumor in the bone, bone
cluding 4 mg of dexamethasone orally twice a day; 20 mg collapse, or nerve damage. Referred pain is common: cer-
of famotidine orally once a day; 50 g/h of fentanyl through vical compressions often cause midscapular pain, thoracic
a transdermal patch that was changed every 3 days; and 4 compressions can cause hip or lumbosacral pain,5 and lum-
mg of hydromorphone orally every 4 hours as needed for bosacral compressions can cause thoracic pain.6 Sixty per-
pain, she underwent revision posterior surgery with lami- cent of the metastases are thoracic, 30% lumbosacral, and
nectomies of the T6 through T8 vertebrae and excision of 10% cervical.3 Commonly, breast and lung cancers cause tho-
tumor from the dorsal aspect of the spine followed by in- racic lesions, while colon and pelvic carcinomas affect the
strumented spinal fusion from the T3 to L2 vertebrae. Five lumbosacral spine.7 In 20% of patients, cancer presents as
days later, she underwent corpectomies of the T6 to T8 ver- a spinal cord compression.5,8
tebrae with resection of epidural tumor and anterior col- Patients with cauda equina syndrome experience dimin-
umn reconstruction from the T5 to T9 vertebrae using a cage, ished sensation over the buttocks, posterior-superior thighs,
rods, and structural rib. Eight days after the anterior sur- and perineal region, and, in 20% to 80%, decreased anal
gery, Ms H was transferred to a rehabilitation facility where sphincter tone. Urinary retention and overflow inconti-
she stayed for 3 weeks. Five months later, she required only nence are pathognomonic of the syndrome (90% sensitiv-
nonopioid medications, had good strength and propriocep- ity; 95% specificity).9 Absence of a postvoid residual virtu-
tion, and was walking more than 2 miles daily. ally excludes it (99.99% negative predictive value ).9
Common signs of spinal cord compression include radicu-
PERSPECTIVES lopathy, weakness,10 sensory changes (eg, paresthesias, loss
Ms H and Dr O were interviewed by a Perspectives editor of sensation), sphincter incontinence, and autonomic dys-
in March 2007. function (eg, urinary hesitancy, retention). One useful scale
MS H: I was lying around . . . not doing a lot, so I started to for functional assessment is the Frankel grading system11
atrophy. . . . I didnt go to work. . . . My social activities were which consists of (A) complete paraplegia, (B) only sen-
cut to nothing, and Im a very active person. I didnt go to bas- sory function, (C) nonambulation, (D) ambulation, and (E)
ketball games, and I missed a football game. I just couldnt go. no neurological symptoms or signs. Other scales include the
DR O: [She] had been a very active woman. Unfortunately, Frankel/American Spinal Injury Association scale,12 the Inter-
with her tumors progressive involvement of the spine, and her national Medical Society of Paraplegia scale,12 and the Tomita
progressive deformity, she became disabled to the point where scale.13 The Barthel index, originally designed for geriatric
she was not really able to ambulate around the house. . . . She patients, additionally assesses transfer from bed to chair or
was only 55 years old and she was really losing her indepen- commode and bowel and bladder function.14
dence. This is always an issue, even for older patients, but for It is difficult to determine the current prevalence of these
someone this age, this is a very difficult thing. signs of spinal cord compression because most studies were
About 500 000 patients die of cancer annually. Ms H is conducted before diagnosis by magnetic resonance imaging
among the 12 700 cancer patients in the United States who, (MRI) became available. In 1 study, 60% to 85% of patients
each year, develop spinal cord compression, putting them at diagnosis had weakness and two-thirds were nonambu-
at risk for pain, paraparesis or paralysis, incontinence, and latory.3 In others, more than half presented with sensory
institutionalization.1 Breast, prostate, and lung cancer each changes beginning in the toes15 or 1 to 5 levels below the
account for 15% to 20% of cases; non-Hodgkin lymphoma, lesion.3 About half needed Foley catheters,3 but autonomic
myeloma, and renal cell carcinoma each account for 5% to dysfunction was never the sole presenting symptom.7,15
10% of cases. The remainder are primarily from colorectal
cancer, cancer of unknown primary, and sarcoma.2,3 Diagnosis of Spinal Cord Compression
DR O: Her main risk for mortality was progressive paraple-
Assessment of Spinal Cord Compression gia. . . . The real risk factors here are infection problems, pul-
MS H: At first it was just pain. After they diagnosed it, it gradu- monary problems, skin problemsthats what leads to death
ally got worse. I started getting numbness in my feet and by in many of these cases, even more so than the progression of
the time I [flew] up to my surgery, they were practically car- the tumor itself.
rying me through security. I could hardly even walk. Delay in diagnosis of spinal cord compression results in
DR O: When she came to see me, she had progressive pain loss of mobility,16,17 bladder dysfunction,16 and decreased sur-
as well as difficulty walking [and] difficulty sitting. . . . [In]a vival.18-22 Because therapy is usually well tolerated in am-
patient presenting with a new onset of [back] pain, especially bulatory patients (even those with very limited overall prog-
a patient with a history of tumor, we always have to have tu- noses),23 the diagnosis of spinal cord compression should
mor very high on our differential diagnosis. always be considered urgent.
938 JAMA, February 27, 2008Vol 299, No. 8 (Reprinted) 2008 American Medical Association. All rights reserved.

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MALIGNANT SPINAL CORD COMPRESSION

Magnetic resonance imaging is the gold standard in de- Pain Management and Symptomatic Measures
tecting epidural metastatic disease and frank spinal cord com- TABLE 1 lists common opioids and adjuvants that control neu-
pression4,19,24,25 (sensitivity 93%, specificity 97%, overall ac- ropathic and bone pain from vertebral metastases and spinal
curacy 95%).26 Plain spine radiographs have inadequate cord compression.3,6,34,35 Opioid dosages shown are for opioid-
sensitivity and a false-negative rate of 10% to 17%.3 No vali- nave patients; those already taking opioids may need sub-
dated predictive models suggest that clinicians can omit an stantially higher dosages. Patients who have moderate or se-
MRI in a patient with known cancer and back pain.27 vere pain often benefit from a continuous intravenous infusion
Finding unsuspected lesions is not unusual.5,28,29 In 45% of of opioids delivered through a patient-controlled analgesia de-
patients, MRI findings altered the radiation therapy field.30 An vice, which allows the patient to self-administer rescue doses
MRI of the entire spine is therefore required, including T1- should the initial basal rate chosen be inadequate or should
weighted sagittal images with T1- or T2-weighted axial images pain occur with movement (so-called incident pain). A con-
in areas of interest.3,19,31 Because patients with prostate cancer sensus document from the American Pain Society offers al-
whohavehadmorethan20bonemetastasesandwhohavetaken gorithms for safe titration of intravenous opioids.35 Cortico-
hormone therapy for several years have a 44% incidence of spi- steroids, effective for both neuropathic and bone pain, are
nal epidural disease, MRIs might be considered even before the discussed below. The anticonvulsants gabapentin and pregaba-
development of symptoms of spinal cord compression.4 lin have been shown to decrease the paresthesias and the burn-
ing, shooting, toothache pain that arises from peripheral nerve
Treatment of Spinal Cord Compression or spinal cord injury,6,33,36,37 although no studies have specifi-
Ms H: All I care about is walking and living my life. cally investigated patients with malignant spinal cord com-
DR O: For many patients, reasonable goals are improve- pression. To minimize sedation, both agents should be started
ment of pain, improvement of quality of life, improvement of at a low dose and titrated to effect (Table 1). Tricyclic anti-
independence. For [other] patients, the goal is to improve sur- depressant agents, which putatively act via a different mecha-
vival. Understanding exactly what the patients goals are and nism than anticonvulsant agents,33 can be used at bedtime be-
understanding the clinical scenario are important for an ap- cause most induce sedation.6,33 Although no randomized trials
propriately guided treatment. have investigated the effects of anticonvulsants in patients with

Table 1. Pharmacologic Management of Pain in Opioid Nave Patients With Malignant Spinal Cord Compression a
Drug Initial Dose for Opioid Comments
Opioids
Morphine b
Immediate release 15-30 mg orally every 2 h as needed Titrate to relief
Sustained release 15 mg orally every 8-12 h Increase every 24 h based on need
Oxycodone b
Immediate release 10-20 mg orally every 2 h as needed Titrate to relief
Sustained release 10 mg orally every 12 h Increase every 24 h based on need
Hydromorphone
Immediate release 4-8 mg orally every 4 h as needed Titrate to relief; add sustained release opioid or fentanyl for
basal relief
Fentanyl 12-25 g/h transdermally every 72 h Add immediate release opioid as needed every 2-4 h
Neuropathic pain adjuvants
Dexamethasone12,32 10 mg orally or intravenous load Current practice; in patients with symptomatic compression,
4-6 mg orally or intravenously every 6 h evidence favors higher doses (see text for discussion)
Gabapentin33 bc 100 mg orally twice a day; 300 mg at bedtime Can cause somnolence, edema, myoclonus
Pregabalin33 bc 75 mg orally twice a day More reliable oral absorption than gabapentin
Amitriptyline, nortriptyline33 d 10-25 mg orally at bedtime Second-line therapy, anticholinergic adverse effects
Bone pain adjuvants
Zoledronic acid12 4 mg intravenously every 3-4 wk Hypocalcemia occurs in patients with vitamin D deficiency
Pamidronate12 90 mg intravenously every 3-4 wk May have less renal toxicity
Acetaminophen 1000 mg orally every 6-8 h
Bowel regimen medications e
Docusate plus senna 1-2 orally twice a day Use in most patients taking opioids
Polyethylene glycol 17-34 g orally at bedtime as needed Used when no stool in 48 h
Bisacodyl or glycerin Daily, scheduled To empty bowel in patients with severe autonomic
suppository dysfunction, suppository followed by enema as needed
Abbreviations: IR, immediate release; SR, sustained release.
a Decrease doses in elderly patients. Table is based on Schiff,3 Abrahm,6 Schmidt et al,32 and Dworkin et al.33
b Decrease doses for creatinine clearance less than 50 mL/min.
c No studies in gabapentin or pregabalin have been reported in patients with malignant spinal cord compression.
d A randomized trial of amitriptyline in patients with spinal cord injury (from unspecified causes) showed no benefit over placebo.
e Goal: soft daily or every-other-day stool without need for Valsalva maneuver.

2008 American Medical Association. All rights reserved. (Reprinted) JAMA, February 27, 2008Vol 299, No. 8 939

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MALIGNANT SPINAL CORD COMPRESSION

malignant spinal cord compression, a single randomized con- end of therapy, 22 of 27 patients taking dexamethasone were
trolled trial involving patients with spinal cord injury (from ambulatory compared with 19 of 30 who did not (P=.046).50
unspecified causes) showed that amitriptyline was no more High-dose dexamethasone to promote posttreatment
effective than placebo.38 ambulation was a grade A recommendation from a 1998
Aggressive treatment of constipation due to autonomic dys- evidence-based guideline.48 However, the guideline acknowl-
function, inactivity, or opioids will prevent increased pain from edged that the optimal dose of dexamethasone is un-
use of the Valsalva maneuver.3,6,35 For patients who retain known.19,24,51 This remains the case a decade later, but given
sphincter control, a typical initial regimen would include a the anxiety, restlessness, and delirium that high doses of dexa-
stool softener, a stimulant, and an osmotic laxative, to promote methasone can induce,52 an initial dexamethasone dose of
soft stooling at least every 1 to 2 days (Table 1). For patients 24 to 40 mg/d orally or intravenously (eg, 6 to 10 mg every
who cannot eliminate stool on their own, a regimen of poly- 6 hours), with a taper during or immediately after comple-
ethylene glycol and a daily stimulant suppository is effective.6 tion of radiation is reasonable.12,32
Bisphosphonates such as zoledronic acid and pamidro- Even at these lower doses, 5% of 21 patients receiving less
nate decrease bone pain.6,12 Nonsteroidal anti-inflammatory than 3 weeks of therapy experienced tremulousness, insom-
agents are safest for younger patients who have no history of nia, delirium, and hyperglycemia.51 Toxicity increased when
gastrointestinal bleeding and normal renal function. They may the total dose exceeded 400 mg and when treatment ex-
be added for patients who poorly tolerate opioid-induced ad- tended for more than 3 weeks.51 Fourteen of 38 patients (37%)
verse effects.6,34,35 Physical therapy will not diminish the pain on the prolonged steroid course developed oral or esopha-
related to tumor or pathological fracture and may accentu- geal Candida infections.51 If a prolonged course of dexameth-
ate fracture pain, so it should not be used before radiation or asone is planned, simultaneous trimethoprim and sulfa-
surgery. Braces, however, may improve comfort by provid- methoxazole to prevent Pneumocystis jiroveci infection53 and
ing external support. 100 mg of fluconazole taken orally daily to prevent thrush
Patients with paraparesis or paralysis frequently experi- and esophageal candidiasis should be considered.
ence anxiety and depression.39 Patients whose core self-
image and sense of self-esteem are predicated upon physi- Radiation Therapy
cal activity and independence may find themselves feeling Radiation therapy is directed at vertebral metastatic sites that
out of control, helpless, and hopeless. They and their fami- are painful or are associated with significant epidural involve-
lies need referrals to social workers, psychologists, psychia- ment or thecal sac indentation (ie, subclinical spinal cord com-
trists, or spiritual leaders. pression). Prospective observational studies have shown that
60% to 90% of patients achieve pain relief with radiation
Glucocorticoid Therapy therapy and dexamethasone.2,20,54,55 From 60% to 100% of
Glucocorticoids reduce injury from traumatic spinal cord patients who are ambulatory before radiation therapy main-
injury40 presumably through their antioxidant or antioxi- tain the ability to walk.2,10,18,19,54 Patients with lung cancer are
dantlike activity, reducing the release of total free fatty ac- least likely to remain ambulatory.2,3 Pooled studies indicate
ids and prostanoids, and preventing lipid hydrolysis and per- that 36%29-31,33-43 to 40%31,33-50 of paraparetic patients become
oxidation.40 Dexamethasone inhibits prostaglandin E241 and ambulatory after radiation therapy.18,20 Restoration of full ambu-
vascular endothelial growth factor production and activ- lation and sphincter function ranges from 13%7-20 to 15%8-23
ity42 and therefore decreases vasogenic edema, which is par- of paralyzed patients.18-20 More than 50% of patients with lung
tially mediated by increased levels of prostaglandin E243 and cancer and 40% with prostate cancer remained paralyzed vs
vascular endothelial growth factor.44 Animal models indi- 10% of patients with breast cancer (P=.003).18
cate a dose-dependent response of vasogenic edema and im- Radiation therapy ports extend 1 or 2 vertebral bodies above
proved neurological function with corticosteroids, even with- and below the site of compression.15 Myelosuppression can
out radiation therapy.45-47 occur if multiple spinal sites are treated.56 Dosing schedules
Although some experts believe that dexamethasone does are designed to have a less than 5% chance of inducing ra-
not benefit asymptomatic ambulatory patients receiving ra- diation myelopathy (ie, hemiparesis, spasticity, and loss of
diation therapy,19,23,48,49 the general consensus is that corti- pain and temperature sensation). Standard external beam ra-
costeroids are beneficial.12,23 Prospective studies suggest an diation therapy usually consists of 30 Gy in 10 fractions48;
initial dexamethasone dose of 96 or 100 mg of intravenous regimens of more than 30 Gy do not improve outcomes.57
bolus followed by 24 mg taken orally 4 times daily for 3 days, However, treatment regimens can be more prolonged (25-40
tapered over 10 days.10,50 Of patients so treated, 64% re- Gy in 10-20 fractions over 2-4 weeks)15; treatment courses
ported substantial relief on day 1 and 82%, overall relief.10 can also be shorter (4 Gy/d for 7 days)18,32; or much shorter
In a randomized single-blind trial, 57 patients receiving ra- (8 Gy once or 4 Gy for 5 sessions, or 8 Gy for 2 sessions 1
diation therapy were randomized by diagnosis (breast can- week apart).56 58,59 After balancing significant pretreatment
cer or other) and gait function (preserved or not) to re- prognostic factors, no regimen has been shown to be supe-
ceive either high-dose or no doses of dexamethasone. At the rior in preserving ambulation.19,24,60
940 JAMA, February 27, 2008Vol 299, No. 8 (Reprinted) 2008 American Medical Association. All rights reserved.

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MALIGNANT SPINAL CORD COMPRESSION

No late radiation-related toxicities have been reported must be able to tolerate staying in the same position for the
using short courses,18,59-61 but patients develop more in- 90 minutes of the treatment.69
field recurrences, less bone recalcification,60 and shortened When used alone (without spinal tumor resection), ra-
survival compared with patients receiving longer courses.62,63 diosurgery provided pain relief in 74%70 to 89%71,72 of pa-
Nevertheless, shorter courses are safe and effective and may tients followed up prospectively for 14 to 48 months.71 None
be particularly appropriate for patients with shorter life ex- developed spinal instability or neurological defects, even
pectancy who can achieve pain control and preserve their though 12% later required surgery for progressive tumor.71
ambulatory status. One prospective cohort study of 500 patients followed up
A new score, derived from a retrospective analysis of more for a median of 21 months (range, 3-53 months) analyzed
than 1800 patients with metastatic spinal cord compres- the outcomes of radiosurgery in patients without bony com-
sion, estimates 6-month survival following radiation pression of neural elements or overt spinal instability.72
therapy.63 Variables associated with a short prognosis in- Long-term pain control was achieved in 86% overall, in 96%
clude primary tumors other than breast, prostate, or my- of patients with breast cancer or melanoma, and in 93% of
eloma and lymphoma; other bone or visceral metastases; non- patients with lung cancer. Tumor progression was halted
ambulatory status before therapy; interval from tumor in 90% of the 65 patients receiving radiosurgery for pri-
diagnosis of less than 15 months; and motor deficits devel- mary treatment (100% of breast, lung, and renal cell carci-
oping less than 14 days before therapy.62,63 Estimates of noma and 75% of melanoma) and in 90% of the 51 patients
6-month survival vary from 4% for patients with all the nega- treated after failure of conventional irradiation (100% of
tive prognostic factors to 99% for those with none.63 Pa- breast and lung carcinoma, 87% of renal carcinomas, and
tients not likely to live long enough for a recurrence or for 75% of melanomas).72 Few studies to date have directly com-
bone recalcification are the best candidates for single frac- pared the efficacy and toxicity of radiosurgery and conven-
tion or short course radiation therapy. tional radiation therapy. One retrospective matched-pair
Overall, 10% of patients treated with standard radiation analysis of patients with spinal metastases from metastatic
therapy develop recurrences in the short term (median time breast cancer showed similar ambulation, performance sta-
to recurrence, 4.5 months),18 but 50% of 2-year survivors tus, and pain control in 18 patients with initial spinal dis-
and almost all 3-year survivors develop recurrences.3 For ease who received CyberKnife radiosurgery and 17 pa-
patients who initially received a short course of therapy, a tients reirradiated for recurrent disease.73
repeat course of external beam radiation therapy (or ste- Insurance coverage for radiosurgery is generally avail-
reotactic radiosurgery as described below) can be consid- able for patients requiring reirradiation but may be more
ered.19 Patients who experience a recurrence have a me- problematic for initial therapy. Further studies comparing
dian survival of 4.2 months, but of those who survive, 88% radiosurgery to traditional radiotherapy are needed to de-
remain ambulatory at 6.5 to 35 months. Radiation- termine its effectiveness and the highest tolerable doses.68,74
induced myelopathy rarely develops (eg, 1 of 13 long-term
survivors59), with a median latency of 1 to 2 years.64 There- Surgery
fore, for patients likely to survive less than 1 year, the ben- DR O: [O]ur goal was to improve her pain and deformi-
efits of reirradiation likely exceed the risks. ty. . . . We can reliably stabilize the spine and that will im-
prove pain, as well as stance and alignment of the spine. . . . Shed
High-Precision Radiotherapy Techniques already had her maximum tolerable dose of radiation, and de-
Advances in radiation therapy techniques show promise both spite radiation, she had progression of tumor. . . . The defor-
for primary treatment and for patients with recurrent mity would continue to get worse over time. . . . In this set-
disease. With the evolution in computed tomography and ting, with the tumor in the epidural space and a revision surgery,
MRI capabilities, conformational radiation therapy plans are were unable to get all the tumor out. By getting a majority of
now 3-dimensional, and, with the advent of intensity- the tumor out, . . . we were able to accurately localize where
modulated radiotherapy (IMRT) (the ability to vary dose de- to go with radiation using the CyberKnife. Its important to rec-
livery during a treatment session), higher radiation doses ognize that there is a role for a multidisciplinary approach to
can now be delivered to the target, sparing normal spinal the patient. . . . We have neuroradiologists who put together some
and paraspinal tissues.65 Image guidance with IMRT is a fur- of the imaging. We have medical oncologists and radiation on-
ther refinement.66 Tomotherapy is a third high-precision tech- cologists. We have our orthopedic team who does complex re-
nique that uses a rotating linear accelerator to deliver IMRT.65 constructions. . . .Having all of these components integrated in
Stereotactic radiosurgery (eg, the CyberKnife65 or the a setting where we are discussing cases and learning from each
Novalis Shaped Beam Surgery64) can be used alone or fol- other is very valuable.
lowing external-beam radiation or surgery, as it was for Ms Debate is ongoing regarding the merits of radiotherapy
H.67 Patients receive 1 large dose (eg, 6-8 Gy) to a localized alone vs surgical therapy followed by radiation for selected
tumor with the precisely shaped radiation beam that comes patients with spinal cord compression. Despite finding few
as close as 1.36 mm to the simulation isocenter.68 Patients papers of high methodological quality,24 a 2005 evidence-
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MALIGNANT SPINAL CORD COMPRESSION

surgical decompression with reconstruction. In observa-


Table 2. Tokuhashi Revised Scoring System for Preoperative
Prognosis of Metastatic Spinal Tumors a tional studies, 80% to 94% of patients obtained pain re-
Parameter Score lief,75,80-82 68% to 75% of nonambulatory patients regained
General condition ambulatory status,75,82 and 50% of severely paraparetic pa-
Poor 0 tients became completely ambulatory.75
Moderate 1 In 2005, Patchell et al79 published the first prospective,
Good 2 randomized trial comparing direct decompressive surgery
No. of extraspinal metastases followed by radiotherapy with radiotherapy alone in a care-
3 0
fully selected subset of patients. Patients had to have MRI
1-2 1
evidence of metastatic epidural spinal cord compression re-
0 2
stricted to a single contiguous area to be eligible, although
No. of vertebral body metastases
3 0 they could have other noncompressive areas of epidural dis-
2 1 ease. Patients had to have a cancer origin other than CNS
1 2 or spinal column, no prior history of cord compression or
Metastases to the major internal organs preexisting neurological disease, at least 1 neurological symp-
Nonremovable 0 tom (eg, pain) or sign, and, if totally paraplegic, for no longer
Removable 1 than 48 hours before study entry.
None 2 Fifty patients were randomized to initial surgery; 3 pa-
Primary site of cancer tients who completed surgery did not receive postopera-
Lung, osteosarcoma, stomach, bladder, 0
esophagus, pancreas tive radiation; 51 patients were randomized to initial radia-
Liver, gallbladder, unidentified 1 tion therapy (30 Gy in 10 fractions), 1 of whom required
Others 2 surgery because of deterioration of strength during radio-
Kidney, uterus 3 therapy. The study was discontinued at its mid point due
Rectum 4 to the superior response of the group randomized to de-
Thyroid, breast, prostate, carcinoid 5 compressive surgery plus radiation therapy. The posttreat-
Palsy or myelopathy ment ambulation rate in those randomized to combination
Complete 0 treatment was 84% vs 57% in those randomized to radia-
Incomplete 1 tion therapy alone (P=.001; odds ratio [OR], 6.2; 95% con-
None 2 fidence interval [CI], 2.0 -19.8]). Patients who were ran-
a The information in this table is based on Tokuhashi et al.76 The lower the score, the worse
the prognosis. Those scoring from 0 to 8 have a prognosis of less than 6 months to live; domized to surgery plus radiotherapy retained ambulation
a score of 9 to 11, between 6 and 12 months; and a score of 12 to 15, more than a year. for a significantly longer period than patients who were ran-
domized to radiation alone (122 vs 13 days, P=.003), and
94% of patients who were ambulatory before surgery plus
based review recommended radiation for ambulatory patients radiotherapy remained ambulatory, while only 76% of pa-
without spinal instability, bony compression, or paraple- tients who were randomized to radiation alone did so. Main-
gia on presentation; it recommended surgery for patients tenance of continence, functional scores, and survival were
with progressive neurological deficits, vertebral column in- also significantly greater in the group randomized to sur-
stability, radioresistant tumors (lung, colon, renal cell), and gery before radiation therapy. Importantly, the efficacy of
intractable pain unrelieved by radiation therapy.18,24,48,75 radiation therapy alone in the study by Patchell et al was
Physicians must weigh the patients health, ability to tol- far less than that seen in unselected patient series. Sug-
erate surgery, and goals of therapy. Surgeons generally agree gested explanations included exclusion of patients with
that a life expectancy of more than 3 months is required for highly radiosensitive tumors from the study,83 inclusion of
spinal surgery and use the scoring system developed by Toku- fewer patients with more fast-growing and potentially ra-
hashi et al76 to predict it (TABLE 2). Several trials have con- diosensitive tumors in the radiotherapy group,84 and a higher
firmed the accuracy of this scoring system, including pa- proportion of patients with vertebral body collapse or with
tients with metastatic breast or renal cell cancers.77,78 The nonneurological morbidity in the radiotherapy group.85 The
prognostic scoring system developed by Rades et al,63 de- authors later provided data refuting the latter 2 explanations.86
veloped from patients receiving radiation therapy, might be Rates of surgical complications (wound breakdown, fail-
applicable as well. ure of spinal stabilization, infection, excessive blood loss,
Prior to the 1980s, laminectomy was the generally ac- respiratory failure, intra-abdominal vascular or visceral in-
cepted surgical approach, but it not only inadequately de- jury, or cerebrospinal fluid leak) range from 23% to 50%.75
compresses the spinal canal, it potentially compromises ver- Complication rates are significantly (P . 001) related to
tebral column stability.79 Currently, surgeons use anterior age older than 65 vs younger than 65 years (71% vs 43%),
(transthoracic and retroperitoneal) and posterolateral ap- history of prior radiation therapy (67% vs 33%),79,81,87 and
proaches (costotransversectomy, lateral extracavitary) for paraparesis vs ambulatory status (64% vs 39%).79,81,87
942 JAMA, February 27, 2008Vol 299, No. 8 (Reprinted) 2008 American Medical Association. All rights reserved.

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MALIGNANT SPINAL CORD COMPRESSION

A recent meta-analysis confirmed that patients with symp- tate or lung cancer is only 4 and 1.5 months, respectively.1
tomatic spinal cord compression who underwent surgery (with One-year survival rates for patients with spinal cord compres-
or without preoperative or postoperative adjunctive radia- sion due to multiple myeloma, lymphoma, and breast and pros-
tion therapy) were 1.3 times more likely to be ambulatory tate cancers were 39%, 38%, 27%, and 22%, respectively, while
(crude risk ratio [cRR], 1.28; 95% CI, 1.20-1.37; P.001) that of lung cancer patients was 4%.1
than patients treated primarily with radiation.88 Although ra- Retrospective and prospective observational studies dem-
diation remains the therapy offered to most patients,89 sur- onstrate that median survival for patients who could walk
gery is increasingly being offered to patients with metastatic after the completion of therapy was 7.9 to 9 months, but
spinal cord compression who fulfill the strict criteria of the median survival for nonambulatory patients was only 1 to
study by Patchell et al. Given that these patients commonly 2 months.18,20,21 Patients with cancer who develop spinal cord
require urgent surgery, the surgical teams at the tertiary can- compression spend twice as many days in the hospital dur-
cer centers who perform these procedures may need to de- ing the last year of life compared with those without spinal
velop new systems to enable them to fit these complex re- cord compression.1
constructive procedures into their surgical schedules.90 The medical oncology team can help patients with spi-
nal cord compression decide which mode of therapy, if any,
Chemotherapy and Hormonal Therapy is appropriate for them by exploring the patients goals, the
Because the epidural space is on the systemic side of the blood likely outcomes of each therapy (eg, pain relief or preser-
brain barrier, chemotherapy and hormonal therapies have been vation or return of function), the beneficial and adverse ef-
used in individual patients with spinal cord compression from fects of therapy, the likely duration of inpatient and reha-
Hodgkin and non-Hodgkin lymphomas,91,92 germ cell tu- bilitation stays, and the estimated survival times with and
mors,93 breast or prostate carcinomas, or neuroblastomas.3 without therapy. For patients, like Ms H, aggressive pallia-
In these individual case reports, the compression com- tive surgery plus radiation therapy will markedly improve
pletely resolved in 5 of the 7 patients reported. No large case the quality of the time remaining. Arranging a multidisci-
series or randomized controlled trials have been reported. plinary consultation with a radiation oncologist and a sur-
geon can help patients and families make their best choice.
Prognosis of Patients With Spinal Cord Compression
DR O: The outcomes are different for patients with solitary me- Rehabilitation
tastases vs patients with widely metastatic disease. For some- DR O: Its important to help the patient make informed choices,
body with widely metastatic disease, in general, our focus is and understand exactly what kind of effect this surgery is go-
on improving health-related quality of life. . . .Were not af- ing to have on their life and what their needs will be after sur-
fecting the natural history of the tumor. We improve mortality gery. They will need immediate rehabilitation. We try to iden-
by improving ambulation and the comorbidities that can oc- tify what kind of resources the patient will have among family
cur with progressive loss of function. and friends, and try to mobilize those resources and try to op-
MS H: I know that cancer is going to get me eventually. I timize whats available to the patient.
have a nodule in my lung that Im not even thinking about right MS H: I had gone through surgery before and I was fine.
now. Im not worrying about it right now. I just dont get into I just tootled along. So, this time I was surprised at how weak
that prognosis stuff. All I care about is walking and living my I was and [at] my inability to walk afterwards. . . . At first, I
life. Im more interested in quality than quantity. couldnt even get over to the commode by myself. . . . By the time
Pretreatment ambulatory status and time from develop- I left the rehab unit, I [could] climb 8 steps and . . . walk about
ment of motor deficits to radiotherapy are the most impor- 100 feet, then sit down and rest, then walk further.
tant predictors of ambulation after treatment.60,94-96 Overall, Rehabilitation is helpful whether the patient is treated with
75% to 100% of ambulatory patients remain ambula- radiation, surgery, or both. Critical to the success of reha-
tory,3,19,54 and 50% of those who survive 1 year are still am- bilitation efforts is integration of patient and support group
bulatory.3 About 14% to 35% of paraparetic and 15% of para- and family efforts with those of the multidisciplinary team.
lyzed patients regain useful function after radiation therapy.4,19 In rehabilitation units, paraplegic patients with bowel and
Median survival after spinal cord compression depends on bladder incontinence receive instruction in transfers, in-
the patients tumor type, ambulatory status, and number and centive spirometry, nutrition, bowel and bladder care, and
site of metastases.62,94-96 Patients with a single metastasis, a ra- skin care.98 Ambulatory patients receive strength and mo-
diosensitive tumor, or with myeloma, breast, or prostate can- bility training. Along with this improved strength, the mul-
cer have the longest survival,3,18,58,97 while patients with mul- tilevel fixation achieved by modern spinal instrumentation
tiple metastases, visceral or brain metastases, or lung or has made postoperative bracing optional99; it does not lead
gastrointestinal cancers have the shortest.3,18,75 Even patients to a higher spinal fusion rate or improve pain relief.
with responsive tumors, such as myeloma, lymphoma, and Observational studies have shown that patients with spi-
breast cancer, have relatively short median survivals of 6.4, nal cord compression who receive rehabilitation have in-
6.7, and 5 months, respectively; survival of patients with pros- creased satisfaction with life, less depression, and persistent
2008 American Medical Association. All rights reserved. (Reprinted) JAMA, February 27, 2008Vol 299, No. 8 943

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MALIGNANT SPINAL CORD COMPRESSION

decreases in pain.98,100 In 1 study, average length of inpatient tion. Although all patients benefit from identification of their
rehabilitation was 27 days; 84% of patients were discharged goals, counseling, and symptomatic treatment and although
to home; and mobility, ambulation, self-care, and transfer abili- most receive corticosteroids, advances in radiation and sur-
ties persisted for at least 3 months following discharge.101 gical techniques and refinements of prognosis are beginning
to enable individualization of specific therapy to maximize
Palliative Care quality and length of life. Radiation therapy alone is offered
Oncologists and palliative care clinicians can also help pa- to the majority of patients. Even patients with a very limited
tients and families begin to explore and cope with changes prognosis may be appropriate candidates for single-fraction
in self-image, independence, roles in the family and com- external-beam radiation therapy or radiosurgery to decrease
munity, and living arrangements. Questions to help the cli- their pain, preserve their ambulation and their ability to trans-
nician understand the patient better include the following: fer, and maintain bowel and bladder function. These pa-
Help me understand what a typical day at home (work, tients may also be appropriate for referral to palliative care
school, etc) was like for you before the (pain, weakness, or hospice programs, as are patients who are not ambulatory
numbness) started. What are the things you need to get done? after radiotherapy. Patients meeting the Patchell criteria should
What do you really enjoy doing? be considered for surgery followed by radiation therapy.
Have you ever needed help to take care of yourself be- Whichever path is chosen, multidisciplinary teams remain
fore, or has it happened to anyone close to you? How did central to providing support and care for patients with spi-
you deal with that? Did you see a counselor? Did your cler- nal cord compression and their families.
gyman or religious community support you? Author Affiliations: Department of Medical Oncology, Division of Psychosocial
Do you know anyone who had to use a cane or a wheel- Oncology, and Palliative Care, Harvard Medical School, Dana-Farber Cancer In-
stitute, and Brigham and Womens Hospital (Dr Abrahm) and Department of Or-
chair to get around? How did you feel about that? How do thopedic Surgery, Harvard Combined Orthopedics Program (Dr Banffy) and De-
you think it might make you feel? partment of Orthopedic Surgery (Dr Harris), Brigham and Womens Hospital, Harvard
Medical School, Boston, Mass.
If you werent able to walk on your own, what would it Financial Disclosures: Dr Abrahm reports that she is a member of the speakers
take for you to be able to stay at home? Who is there to help bureau for Merck and Purdu Pharma and is on the advisory board for Endo Phar-
during the day and overnight? maceuticals and Wyeth. No other conflicts were reported
Funding/Support: The Perspectives on Care at the Close of Life section is made
For patients with limited prognoses, clinicians should also possible by a grant from the California HealthCare Foundation.
help the patient and family identify health care proxies and Role of the Sponsors: The funding source had no role in the preparation, review,
or approval of the manuscript.
delineate preferences regarding cardiopulmonary resusci- Other Resources: For a list of related references, see http://www.jama.com.
tation. Questions to help in doing this include: Additional Contributions: We thank Harvey Mamon, MD, PhD, Department of
Radiation Oncology, Harvard Medical School, and Department of Oncology, Brigham
Whom do you regularly consult about important issues? Is and Womens Hospital, for his helpful reading of the manuscript, for which he
there one person who really understands what is important to received no compensation.
you and how you make your choices about treatments?
If, at sometime in the future, you werent able to tell us REFERENCES
directly what you wanted, should we talk with them? They 1. Loblaw DA, Laperriere NJ, Mackillop WJ. A population-based study of malig-
would be what we call a health care proxy. We would ask nant spinal cord compression in Ontario. Clin Oncol (R Colleg Radiol). 2003;
15(4):211-217.
them to tell us what they think you would want us to do. 2. Turner S, Marosszeky B, Timms I, Boyages J. Malignant spinal cord compres-
Given their short median survival, this work is espe- sion: a prospective evaluation. Int J Radiat Oncol Biol Phys. 1993;26(1):141-
146.
cially important for patients with spinal cord compression 3. Schiff D. Spinal cord compression. Neurol Clin. 2003;21(1):67-86.
due to lung or gastrointestinal cancers (especially those with 4. Bayley A, Milosevic M, Blend R, et al. A prospective study of factors predicting
clinically occult spinal cord compression in patients with metastatic prostate carcinoma.
multiple metastases), or any patient who is nonambulatory Cancer. 2001;92(2):303-310.
after surgery or radiation therapy. By refocusing efforts from 5. Levack P, Graham J, Collie D, et al; Scottish Cord Compression Study Group.
disease-oriented therapies to creating legacies and bring- Dont wait for a sensory levellisten to the symptoms: a prospective audit of the
delays in diagnosis of malignant cord compression. Clin Oncol (R Colleg Radiol).
ing closure to their personal relationships, oncology teams 2002;4:472-480.
can reassure patients and their families that they will not 6. Abrahm JL. A Physicians Guide to Pain and Symptom Management in Cancer
Patients. 2nd ed. Baltimore, MD: Johns Hopkins University Press; 2005.
be abandoned. Oncologists can remain the patients physi- 7. Posner JB. Neurologic Complications of Cancer. Philadelphia, PA: Davis Pub-
cian in hospice programs, and for patients whose needs ex- lishing; 1995.
8. Schiff D, ONeill BP, Suman VJ. Spinal epidural metastases as the initial mani-
ceed those that hospice programs can provide, palliative care festation of malignancy: clinical features and diagnostic approach. Neurology. 1997;
teams can help oncology teams provide care and comfort 49(2):452-456.
during the final months. 9. Deyo R, Rainville J, Kent D. What can the history and physical examination tell
us about low back pain? JAMA. 1992;286:760-765.
10. Greenberg HS, Kim JH, Posner JB. Epidural spinal cord compression from meta-
CONCLUSION static tumor: results with a new treatment protocol. Ann Neurol. 1980;8(4):361-
366.
Diagnosis of epidural spinal cord compression is an emer- 11. Frankel HL, Hancock DO, Hyslop G, et al. The value of postural reduction in
gency. Survival and quality of life are directly related to the the initial management of closed injuries of the spine with paraplegia and tetraple-
gia. I. Paraplegia. 1969;7(3):179-192.
patients pretreatment ambulatory status. Emergency MRI and 12. Rades D, Schild SE. Spinal cord compression. Eur J Cancer. 2007;5(suppl):
immediate initiation of specific therapy may preserve func- 359-370.

944 JAMA, February 27, 2008Vol 299, No. 8 (Reprinted) 2008 American Medical Association. All rights reserved.

Downloaded from www.jama.com at McGill University Libraries, on March 1, 2008


MALIGNANT SPINAL CORD COMPRESSION

13. Tomita T, Galicich JH, Sundaresan N. Radiation therapy for spinal epidural me- 40. Bracken MB, Shepard MJ, Holford TR, et al; National Acute Spinal Cord In-
tastases with complete block. Acta Radiol Oncol. 1983;22(2):135-143. jury Study. Administration of methylprednisolone for 24 or 48 hours or tirilazad
14. Makris A, Kunkler IH. The Barthel Index in assessing the response to palliative mesylate for 48 hours in the treatment of acute spinal cord injury: results of the
radiotherapy in malignant spinal cord compression: a prospective audit. Clin On- Third National Acute Spinal Cord Injury Randomized Controlled Trial. JAMA. 1997;
col (R Coll Radiol). 1995;7(2): 82-86. 277(20):1597-1604.
15. Quinn JA, DeAngelis LM. Neurologic emergencies in the cancer patient. Se- 41. Siegal T, Siegal T, Shohami E, Shapira Y. Comparison of soluble dexametha-
min Oncol. 2000;27(3):311-321. sone sodium phosphate with free dexamethasone and indomethacin in treatment
16. Husband DJ. Malignant spinal cord compression: prospective study of delays of experimental neoplastic spinal cord compression. Spine. 1988;13(10):1171-
in referral and treatment. BMJ. 1998;317(7150):18-21. 1176.
17. Mitera G, Loblaw A. Delays from symptom onset to treatment in malignant 42. Gonzalez MV, Gonzalez-Sancho JM, Caelles C, Munoz A, Jimenez B. Hormone-
spinal cord compression: quantification and effect on pre-treatment neurological activated nuclear receptors inhibit the stimulation of the JNK and ERK signaling
status: Canadian Association of Radiation Oncology Annual Meeting. Radiother pathways in endothelial cells. FEBS Lett. 1999;459(2):272-276.
Oncol. 2003;69(suppl 1):141. 43. Daw HA, Markman M. Epidural spinal cord compression in cancer patients:
18. Helweg-Larsen S, Sorensen PS, Kreiner S. Prognostic factors in metastatic spi- diagnosis and management. Cleve Clin J Med. 2000;67(7):497-501-504.
nal cord compression: a prospective study using multivariate analysis of variables 44. Hayashi T, Sakurai M, Abe K, et al. Expression of angiogenic factors in rabbit
influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. spinal cord after transient ischaemia. Neuropathol Appl Neurobiol. 1999;25(1):
2000;46(5):1163-1169. 63-71.
19. Loblaw DA, Laperriere N, Perry J, Chambers A; Neuro-oncology Disease Site 45. Ushio Y, Posner R, Posner JB, Shapiro WR. Experimental spinal cord compres-
Group. Malignant extradural spinal cord compression: diagnosis and management. sion by epidural neoplasm. Neurology. 1977;27(5):422-429.
http://www.cancercare.on.ca/pdf/pebc9-9esf.pdf. Updated January 2004. Ac- 46. Delattre J-Y, Arbit E, Thatler HT, Rosenblum MK, Posner JB. A dose-response
cessed October 28, 2007. study of dexamethasone in a model of spinal cord compression caused by epidu-
20. Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in ral tumor. J Neurosurg. 1989;70(6):920-925.
metastatic spinal cord compression. Final results from a prospective trial. Int J Ra- 47. Ushio Y, Posner R, Kim JH, Shapiro WR, Posner JB. Treatment of experimen-
diat Oncol Biol Phys. 1995;32(4):959-967. tal spinal cord compression caused by extradural neoplasms. J Neurosurg. 1977;
21. Maranzano E, Bellavita R, Rossi R, et al. Short-course versus split-course ra- 47(3):380-390.
diotherapy in metastatic spinal cord compression: results of a Phase III, random- 48. Loblaw DA, Smith K, Lockwood G, Laperriere N. The Princess Margaret Hos-
ized, multicenter trial. J Clin Oncol. 2005;23(15):3358-3365. pital experience of malignant spinal cord compression (abstract). Proc Am Soc Clin
22. Chataigner H, Onimus M. Surgery in spinal metastasis without spinal cord com- Oncol. 2003;22:119.
pression; indications and strategy related to the risk of recurrence. Eur Spine J. 49. Maranzano E, Latini P, Beneventi S, et al. Radiotherapy without steroids in
2000;9(6):523-527. selected metastatic spinal cord compression patients: a Phase II trial. Am J Clin
23. Prasad D, Schiff D. Malignant spinal-cord compression. Lancet Oncol. 2005; Oncol. 1996;19(2):179-183.
6(1):15-24. 50. Sorensen S, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high-dose
24. Loblaw DA, Perry J, Chambers A, Laperriere NJ. Systematic review of the di- dexamethasone in carcinomatous metastatic spinal cord compression treated with
agnosis and management of malignant extradural spinal cord compression: the radiotherapy: a randomized trial. Eur J Cancer. 1994;30A(1):22-27.
Cancer Care Ontario Practice Guidelines Initiatives Neuro-Oncology Disease Site 51. Weissman DE, Dufer D, Vogel V, Abeloff MD. Corticosteroid toxicity in neuro-
Group. J Clin Oncol. 2005;23(9):2028-2037. oncology patients. J Neurooncol. 1987;5(2):125-128.
25. Ruckdeschel JC. Rapid, cost-effective diagnosis of spinal cord compression due 52. Breitbart W, Stiefel F, Kornblith AB, Pannullo S. Neuropsychiatric disturbance in
to cancer. Cancer Control. 1995;2(4):320-323. cancer patients with epidural spinal cord compression receiving high dose cortico-
26. Li KC, Poon PY. Sensitivity and specificity of MRI in detecting malignant spi- steroids (a prospective comparison study). Psychooncology. 1993;2:233-245.
nal cord compression and in distinguishing malignant from benign compression 53. Slivka A, Wen PY, Shea WM, Loeffler JS. Pneumocystis pneumonia during
fractures of vertebrae. Magn Reson Imaging. 1988;6(5):547-556. steroid taper with primary brain tumours. Am J Med. 1993;94(2):216-219.
27. Kienstra GEM, Terwee CB, Dekker FW, et al. Prediction of spinal epidural 54. Helweg-Larsen S. Clinical outcome in metastatic spinal cord compression; a
metastasis. Arch Neurol. 2000;57(5):690-695. prospective study of 153 patients. Acta Neurol Scand. 1996;94(4):269-275.
28. Bonner JA, Lichter AS. A caution about the use of MRI to diagnose spinal cord 55. Katagiri H, Takahashi M, Inagaki J, et al. Clinical results of non-surgical treat-
compression. N Engl J Med. 1990;322(8):556-557. ment for spinal metastases. Int J Radiat Oncol Biol Phys. 1998;42(5):1127-1132.
29. Rodichok LD, Ruckdeschel JC, Harper GR, et al. Early detection and treat- 56. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain.
ment of spinal epidural metastases: the role of myelography. Ann Neurol. 1986; 1997;69(1-2):1-18.
20(6):696-702. 57. Rades D, Karstens JH, Hoskin PJ, et al. Escalation of radiation dose beyond 30
30. Colletti PM, Siegal HJ, Woo MY, Young HY, Terk MR. The impact on treat- Gy in 10 fractions for metastatic spinal cord compression. Int J Radiat Oncol Biol
ment planning of MRI of the spine in patients suspected of vertebral metastasis: Phys. 2007;67(2):525-531.
an efficacy study. Comput Med Imaging Graph. 1996;20(3):159-162. 58. Bauer HC, Wedin R. Survival after surgery for spinal and extremity metasta-
31. Kim JK, Learch TJ, Colletti PM, Lee JW, Tran SD, Terk MR. Diagnosis of ver- ses: prognostication in 241 patients. Acta Orthop Scand. 1995;66(2):143-146.
tebral metastasis, epidural metastasis, and malignant spinal cord compression: are 59. Maranzano E, Bellavita R, Floridi P, et al. Radiation-induced myelopathy in
T1-weighted sagittal images sufficient? Magn Reson Imaging. 2000;18(7):819- long-term surviving metastatic spinal cord compression patients after hypofrac-
824. tionated radiotherapy: a clinical and magnetic resonance imaging analysis. Radio-
32. Schmidt MH, Klimo P, Vrionis FD. Metastatic spinal cord compression. J Natl ther Oncol. 2001;60(3):281-288.
Compr Canc Netw. 2005;3(5):711-719. 60. Rades D, Stalpers LJA, Veninga T, et al. Evaluation of five radiation schedules
33. Dworkin RH, OConnor AB, Backonja M, et al. Pharmacologic management and prognostic factors for metastatic spinal cord compression. J Clin Oncol. 2005;
of neuropathic pain: elvidence-based recommendations. Pain. 2007;132(3):237- 23(15):3366-3375.
251. 61. Rades D, Veninga T, Stalpers LJA, et al. Outcome after radiotherapy alone
34. Foley KM. Management of cancer pain. In: Devita VT, Hellman S, Rosenberg for metastatic spinal cord compression in patients with oligometastases. J Clin Oncol.
SA, eds. Cancer, Principles and Practice of Oncology. 7th ed. Philadelphia, PA: 2007;25(1):50-56.
Lippincott Williams & Wilkins; 2005:2615-2649. 62. Rades D, Fehlauer F, Schulte R, et al. Prognostic factors for local control and
35. Miaskowski C, Cleary J, Burney R, et al. Guideline for the Management of survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol.
Cancer Pain in Adults and Children, APS Clinical Practice Guideline Series, No. 2006;24(21):3388-3393.
3. Glenview, IL: American Pain Society; 2005. 63. Rades D, Dunst J, Schild SE. The first score predicting overall survival in pa-
36. Levendoglu F, Ogun CO, Ozerbil O, Ogun TC, Ugurlu H. Gabapentin is a tients with metastatic spinal cord compression. Cancer. 2008;112(1):157-161.
first line drug for the treatment of neuropathic pain in spinal cord injury. Spine. 64. Schiff D, Shaw EG, Cascino TL. Outcome after spinal reirradiation for malig-
2004;29(7):743-751. nant epidural spinal cord compression. Ann Neurol. 1995;37:583-589.
37. Siddall PJ, Cousins MJ, Otte A, Griesling T, Chambers R, Murphy TK. Pregaba- 65. Rock JP, Ryu S, Yin F-F, Schreiber F, Abdulhak M. The evolving role of ste-
lin in central neuropathic pain associated with spinal cord injury: a placebo- reotactic radiosurgery and stereotactic radiation therapy for patients with spine
controlled trial. Neurology. 2006;67(10):1792-1800. tumors. J Neurooncol. 2004;69(1-3):319-334.
38. Cardenas DD, Warms CA, Turner JA, Marshall H, Brooke MM, Loeser JD. Ef- 66. Yamada Y, Lovelock DM, Bilsky MH. A review of image-guided intensity-
ficacy of amitriptyline for relief of pain in spinal cord injury: results of a random- modulated radiotherapy for spinal tumors. Neurosurgery. 2007;61(2):226-235.
ized controlled trial. Pain. 2002;96(3):365-373. 67. Rock JP, Ryu S, Shukairy MS, et al. Postoperative radiosurgery for malignant
39. Craig AR, Hancock KM, Dickson HG. Spinal cord injury: a search for deter- spinal tumors. Neurosurgery. 2006;58(5):891-898.
minants of depression two years after the event. Br J Clin Psychol. 1994;33(pt 2): 68. Ryu S, Yin FF, Rock J, et al. Image-guided and intensity modulated radiosur-
221-230. gery for patients with spinal metastasis. Cancer. 2003;97(8):2013-2018.

2008 American Medical Association. All rights reserved. (Reprinted) JAMA, February 27, 2008Vol 299, No. 8 945

Downloaded from www.jama.com at McGill University Libraries, on March 1, 2008


MALIGNANT SPINAL CORD COMPRESSION

69. Rades D, Schild SE. Is stereotactic radiosurgery the best treatment option for 86. Patchell RA, Tibbs PA, Regine WF. Surgical resection in metastatic spinal cord
patients with spinal metastases? Nat Clin Pract Oncol. 2007;4(7):400-401. compression [reply]. Lancet. 2006;367(9505):110.
70. Degen JW, Gagnon GJ, Voyadzis J, et al. CyberKnife sterotactic radiosurgical 87. Ghogawala Z, Mansfield FL, Borges LF. Spinal radiation before surgical de-
treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine. compression adversely affects outcomes of surgery for symptomatic metastatic spi-
2005;2(5):540-549. nal cord compression. Spine. 2001;26(7):818-824.
71. Gerszten PC, Burton SA, Ozhasoglu C, et al. Stereotactic radiosurgery for spi- 88. Klimo P, Thompson C, Kestle J. A meta-analysis of surgery versus conven-
nal metastases from renal cell carcinoma. J Neurosurg Spine. 2005;3:288-295. tional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro
72. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal Oncol. 2005;7(1):64-76.
metastases: clinical experience in 500 cases from a single institution. Spine. 2007; 89. Knisely J, Strugar J. Can decompressive surgery improve outcome in patients
32(2):193-199. with metastatic epidural spinal-cord compression? Nat Clin Pract Oncol. 2006;
73. Gagnon GJ, Henderson FC, Gehan EA, et al. CyberKnife radiosurgery for breast 3(1):14-15.
cancer spine metastases: a matched-pair analysis. Cancer. 2007;110(8):1796- 90. van den Bent MJ. Surgical resection improves outcome in metastatic epidural
1802. spinal cord compression. Lancet. 2005;366(9486):609-610.
74. Ryu S, Jin J, Jin R, et al. Partial volume tolerance of the spinal cord and com- 91. Wong ET, Portlock CS, OBrien JP, De Angelis LM. Chemosensitive epidural spi-
plications of single dose radiosurgery. Cancer. 2007;109(3):628-636. nal cord disease in non-Hodgkins lymphoma. Neurology. 1996;46(6):1543-1547.
75. Sundaresan N, Sachdev VP, Halland JF, et al. Surgical treatment of spinal cord 92. Burch PA, Grossman SA. Treatment of epidural cord compressions from Hodgkins
compression from epidural metastasis. J Clin Oncol. 1995;13(9):2330-2335. disease with chemotherapy. Am J Med. 1988;84(3 pt 1):555-558.
76. Tokuhashi Y, Matsuaki H, Oda H, et al. A revised scoring system for preop- 93. Cooper K, Bajorin D, Shapiro W, Krol G, Sze G, Bosl GJ. Decompression of
erative evaluation of metastatic spine tumor prognosis. Spine. 2005;30(19):2186- epidural metastases from germ cell tumors with chemotherapy. J Neurooncol. 1990;
2191. 8(3):275-280.
77. Ulmar B, Richter M, Cakir B, et al. The Tokuhashi score: significant predictive 94. Rades D, Heidenreich F, Karstens JH. Final results of a prospective study of
value for the life expectancy of patients with breast cancer with spinal metastases. the prognostic value of the time to develop motor deficits before irradiation in meta-
Spine. 2005;30(19):2222-2226. static spinal cord compression. Int J Radiat Oncol Biol Phys. 2002;53(4):975-
78. Ulmar B, Naumann U, Catalkaya S, et al. Prognosis scores of Tokuhashi and 979.
Tomita for patients with spinal metastases of renal cancer. Ann Surg Oncol. 2007; 95. Kim RY, Spencer SA, Meredith RF, et al. Extradural spinal cord compression:
14(2):998-1004. analysis of factors determining functional prognosisprospective study. Radiology.
79. Harrington KD. Anterior decompression and stabilization of the spine as a treat- 1990;176(1):279-282.
ment for vertebral collapse and spinal cord decompression from metastatic 96. Loblaw DA, LaPierre NJ. Emergency treatment of malignant extradural spinal
malignancy. Clin Orthop Relat Res. 1988;233(233):177-197. cord compression: an evidence-based guideline. J Clin Oncol. 1998;16(4):1613-
80. Sundaresan N, Galicich JH, Lane JM, et al. Treatment of neoplastic epidural 1624.
cord compression by vertebral body resection and stabilization. J Neurosurg. 1985; 97. Sioutos PJ, Arbit E, Meshulam CF, Galicich JH. Spinal metastases from solid
63(5):676-684. tumors: analysis of factors affecting survival. Cancer. 1995;76(8):1453-1459.
81. Chen YJ, Chang G, Chen H, et al. Surgical results of metastatic spinal cord 98. Ruff RL, Adamson VW, Ruff SS, et al. Directed rehabilitation reduces pain and
compression secondary to non-small cell lung cancer. Spine. 2007;32(15):E413- depression while increasing independence and satisfaction with life for patients
E418. with paraplegia due to epidural metastatic spinal cord compression. J Rehabil Res
82. Patchell RA, Tibbs PA, Regine WF. Direct decompressive surgical resection in Dev. 2007;44(1):1-10.
the treatment of spinal cord compression caused by metastatic cancer: a random- 99. Connolly PJ, Grob D. Controversy: bracing of patients after fusion for degen-
ized trial. Lancet. 2005;366(9486):643-648. erative problems of the lumbar spineyes or no? Spine. 1998;23(12):1426-
83. Thomas KC, Patchell RA, Nosyk B, Anis A. Be careful in getting cost- 1428.
effectiveness conclusions from a debatable trial! [author reply]. Int J Radiat Oncol 100. Ruff RL, Ruff SS, Wang X. Persistent benefits of rehabilitation on pain and
Biol Phys. 2007;68:314-315. life quality for nonambulatory patients with spinal epidural metastasis. J Rehabil
84. Koch M, De Keyser J. Surgical resection in metastatic spinal cord compression Res Dev. 2007;44(2):271-278.
[letter]. Lancet. 2006;367(9505):109. 101. McKinley WO, Conti-Wyneken AR, Vokac CW. Rehabilitative functional out-
85. Kunkler I. Surgical resection in metastatic spinal cord compression [letter]. Lancet. come of patients with neoplastic spinal cord compression. Arch Phys Med Rehabil.
2006;367(9505):109. 1996;77(9):892-895.

946 JAMA, February 27, 2008Vol 299, No. 8 (Reprinted) 2008 American Medical Association. All rights reserved.

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WEB-ONLY CONTENT

Web Resources for Cancer Care


PATIENT INFORMATION PEOPLE LIVING WITH CANCER sion from the United Kingdom, em-
ABOUT MALIGNANT SPINAL http://www.plwc.org phasizing rehabilitation as an important
CORD COMPRESSION People Living With Cancer is sup- part of the management.
http://www.cancerbackup.org.uk ported by the American Society for
Clinical Oncology; its Web site in- NATIONAL CANCER INSTITUTE
/Resourcessupport/Symptomsside
effects/Othersymptomssideeffects cludes information about pain, pallia- http://www.cancer.gov/clinicaltrials
/Malignantspinalcordcompression tive care, care giving, and coping. /results/spinal-cord-compression0603
Cancerbackups mission is to give Results of the trial comparing
SPINAL CORD INJURY surgery to radiation therapy for
patients with cancer and their families WEB SITES
up-to-date information, practical ad- malignant spinal cord compress-
vice, and support they need. This http://www.spinal-cord.org; http://www ion written in patient-centered lan-
user-friendly Web page provides spe- .aascipsw.org; http://www.makoa.org guage.
cific information about spinal cord com- These sites are for patients with spi-
nal cord injuries and their families. LITERATURE REVIEW
pression. REGARDING MALIGNANT
UNITED KINGDOM SPINAL CORD COMPRESSION.
CANCER CARE INFORMATION http://www.supportiveoncology
http://www.cancercare.org http://www.beatson.scot.nhs.uk/assets .net/journal/articles/0205377
Cancer Care is an organization of so- /pdf/education/MSCC%20Literature .pdf
cial workers who provide free tele- %20Review.pdf Review through 2003 of diagnosis
phone group counseling for patients Patient-oriented information regard- and management of malignant extra-
and caregivers. ing malignant spinal cord compres- dural spinal cord compression.

2008 American Medical Association. All rights reserved. (Reprinted) JAMA, February 27, 2008Vol 299, No. 8 E1

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